chr11-73073628-A-G

Variant names:

• chr11-73073628-A-G
• rs6592508
• NM_014824.3:c.165+10067T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014824.3(FCHSD2):​c.165+10067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,988 control chromosomes in the GnomAD database, including 16,598 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16598 hom., cov: 32)
• Consequence: FCHSD2 NM_014824.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 11 publications found

Genes affected

FCHSD2 (HGNC:29114): (FCH and double SH3 domains 2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in plasma membrane. Colocalizes with clathrin-coated pit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHSD2	NM_014824.3	c.165+10067T>C		intron_variant	Intron 3 of 19	ENST00000409418.9	NP_055639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCHSD2	ENST00000409418.9	c.165+10067T>C		intron_variant	Intron 3 of 19	2	NM_014824.3	ENSP00000386722.4

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68972 AN: 151870 Hom.: 16589 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68985 AN: 151988 Hom.: 16598 Cov.: 32 AF XY: 0.466 AC XY: 34651 AN XY: 74286

African (AFR) AF: 0.323 AC: 13370 AN: 41452

American (AMR) AF: 0.488 AC: 7450 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3209 AN: 5186

South Asian (SAS) AF: 0.650 AC: 3134 AN: 4818

European-Finnish (FIN) AF: 0.654 AC: 6907 AN: 10560

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32213 AN: 67920

Other (OTH) AF: 0.417 AC: 880 AN: 2112

Alfa AF: 0.471 Hom.: 12605

Bravo AF: 0.432

Asia WGS AF: 0.578 AC: 2003 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6592508; hg19: chr11-72784673;